THIS COMPONENT IS ENTITLED CELL-TO-CELL COMMUNICATIONS IN CANCER PROGRAM ABSTRACT The long-term goal of the new Cell-to-Cell Communications in Cancer Program (C4P) is to unravel the complex cellular communication between tumor and non-tumor cells that is pivotal to cancer development, progression and metastasis. Identifying factors (biochemical and physical), the receptive signaling pathways responsible and the cellular basis for this communication will lay the framework for the design of specific therapeutic modalities. C4P includes individuals focused on understanding how stromal cells and extracellular matrix structural proteins, growth factors and cytokines interact with tumor cells to impact the tumorigenic process. The program is primarily a basic discovery-based cancer biology research group that is structured to interface with other programs within Siteman Cancer Center (SCC) that are positioned to translate breakthroughs into patient care through genetics, molecular and cellular cancer biology, and functional genomics. To facilitate interactions between basic researchers within C4P and clinicians, members are organized around three specific cancer areas: (1) unraveling the molecular mechanisms that impact the metastatic process including how stromal cells impact the premetastatic niche and the immune landscape at the metastatic site; (2) lung cancer development, progression, metastasis and treatment; and (3) brain cancer development, progression and treatment. The aims of the C4P are to (1) identify key communication molecules and pathways (i.e., targets) in tumor- stromal interactions that impact tumor cell proliferation, survival and metastasis and then to develop strategies to target these key molecules or pathways; and (2) develop select inter-programmatic working groups that can facilitate translational efforts from results that arise from efforts in Aim 1. Each aim is focused on the central importance of communication in the cancer microenvironment. Each member has specific expertise and shared goals that have been and will continue to be utilized to develop a program with strong and fruitful intra- programmatic and inter-programmatic interactions. C4P has 39 members from 10 departments and 2 schools and is supported by $16.8 million in funding, of which $3.1 million is from NCI and $12.4 is other peer-reviewed funding. Currently, 28% of C4P members are supported by the NCI and 85% are supported by peer-reviewed funding including agencies such as the ACS, AACR, DOD and Komen. Between 2009-2014, C4P members published 663 peer-reviewed papers with 101 of these publications appearing in journals with impact factors above 10. Members also displayed significant interactions as evidenced by the 150 (23%) inter- and 59 (9%) intra-programmatic publications.